Novel Hybrid Molecules of Cholinesterase Inhibitor for Alzheimer’s Disease: A Systematic Review

Acetylcholinesterase (AChE) inhibitor is a basic drug design recently used in treating Alzheimer’s disease (AD). However, butyrylcholinesterase (BuChE) also suggested to be responsible for the hydrolysis of acetylcholine (ACh) and its inhibition may benefit in the latter stage of AD. Nonetheless, the search for potent AChE and BuChE inhibitor is still in need, in curing this neurodegenerative disorders. Numerous hybrid molecules were designed for the dual inhibition of AChE and BuChE. However, these molecules have different selectivity towards AChE and BuChE. Therefore, this systematic review aims to determine a rational design that can exhibit high inhibition against AChE and BuChE activity. ScienceDirect, Pubmed, Medline & Ovid and ISI Web of Science database from January 2006 to September 2016 were searched systematically with some specific inclusive and exclusive criterias. The synthesis of hybrid molecules and anticholinesterase (AChE and BuChE) test conducted in human AChE and BuChE with IC50 values were included in this review. Two reviewers independently evaluated the studies and extracted the data using a standardized data collection form. Only one study was identified from the search with IC50 value recorded lower than rivastigmine. Compound 1 (showed high inhibition against AChE (IC50 = 0.34 μM) and BuChE (IC50 = 0.88 μM). This review has successfully determined a novel hybrid molecule containing 2-arylbenzofuran skeleton, which possess dual inhibition of anticholinesterase for neurodegenerative disorders especially Alzheimer disease.